NDLI: Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant

Content Provider	Springer Nature Link
Author	Lauria, Antoni Ippolito, Mario Almerico, Anna Maria
Copyright Year	2007
Abstract	The emergence of drug-resistant mutants of HIV-1 is a tragic effect associated with conventional long-treatment therapies against acquired immunodeficiency syndrome. These mutations frequently involve the aspartic protease encoded by the virus; knowledge of the molecular mechanisms underlying the conformational changes of HIV-1 protease mutants may be useful in developing more effective and longer lasting treatment regimes. The flap regions of the protease are the target of a particular type of mutations occurring far from the active site. These mutations modify the affinity for both substrate and ligands, thus conferring resistance. In this work, molecular dynamics simulations were performed on a native wild type HIV-1 protease and on the drug-resistant M46I/G51D double mutant. The simulation was carried out for a time of 3.5 ns using the GROMOS96 force field, with implementation of the SPC216 explicit solvation model. The results show that the flaps may exist in an ensemble of conformations between a “closed” and an “open” conformation. The behaviour of the flap tips during simulations is different between the native enzyme and the mutant. The mutation pattern leads to stabilization of the flaps in a semi-open configuration.
Starting Page	1151
Ending Page	1156
Page Count	6
File Format	PDF
ISSN	16102940
Journal	Journal of Molecular Modeling
Volume Number	13
Issue Number	11
e-ISSN	09485023
Language	English
Publisher	Springer-Verlag
Publisher Date	2007-09-06
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	HIV-1 protease Molecular dynamics simulations Flap motions HIV-1 drug-resistant mutants Gromacs 3.2 Computer Application in Life Sciences Life Sciences Health Informatics Molecular Medicine Biomedicine general Computer Applications in Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Physical and Theoretical Chemistry Computational Theory and Mathematics Catalysis Inorganic Chemistry Computer Science Applications

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations

Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease

Insights into the functional role of protonation states in the HIV-1 protease-BEA369 complex: molecular dynamics simulations and free energy calculations

Insights into the structural function of the complex of HIV-1 protease with TMC-126: molecular dynamics simulations and free-energy calculations

Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: Free energy calculation and molecular dynamic simulation

Molecular motions of human HIV-1 gp120 envelope glycoproteins

Insights derived from molecular dynamics simulation into the molecular motions of serine protease proteinase K

Insights into the high fidelity of a DNA polymerase I mutant

Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation

Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant

Similar Documents

Insights into amprenavir resistance in E35D HIV-1 protease mutation from molecular dynamics and binding free-energy calculations

Effects of the V82A and I54V mutations on the dynamics and ligand binding properties of HIV-1 protease

Insights into the functional role of protonation states in the HIV-1 protease-BEA369 complex: molecular dynamics simulations and free energy calculations

Insights into the structural function of the complex of HIV-1 protease with TMC-126: molecular dynamics simulations and free-energy calculations

Insights into drug resistance of mutations D30N and I50V to HIV-1 protease inhibitor TMC-114: Free energy calculation and molecular dynamic simulation

Molecular motions of human HIV-1 gp120 envelope glycoproteins

Insights derived from molecular dynamics simulation into the molecular motions of serine protease proteinase K

Insights into the high fidelity of a DNA polymerase I mutant

Differential Flap Dynamics in Wild-type and a Drug Resistant Variant of HIV-1 Protease Revealed by Molecular Dynamics and NMR Relaxation

Molecular dynamics studies on HIV-1 protease: a comparison of the flap motions between wild type protease and the M46I/G51D double mutant